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3-Benzisothiazolylpiperazine derivatives as potential atypical antipsychotic agents
Authors:HR Howard  JA Lowe  TF Seeger  PA Seymour  SH Zorn  PR Maloney  FE Ewing  ME Newman  AW Schmidt  JS Furman  GL Robinson  E Jackson  C Johnson  J Morrone
Affiliation:Institute for Medical Chemistry and Biochemistry, University of Innsbruck, Austria.
Abstract:90K is a tumor-associated antigen. Using myelomonocytic cell line THP-1 we determined neopterin production and tryptophan degradation after exposure of cells to 90K in the presence and the absence of interferon-gamma. Interferon-gamma is a well known stimulus for THP-1 cells inducing e.g. neopterin production and tryptophan degradation. Treatment of cells with 50 micrograms/ml 90K induced significant neopterin formation, and the exposure of cells to 90K in addition to 100 U/ml interferon-gamma amplified neopterin production compared to the sole effect of interferon-gamma. In parallel, a significant degradation of tryptophan was observed in culture supernatants leading to the formation of kynurenine. When the cells were treated with the combination of 90K and interferon-gamma the degradation of tryptophan was further enhanced. The data demonstrate that tumor-associated antigen 90K interferes with immunocompetent target cells and is able to induce a biochemical response in monocytic cells.
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